FDA Approves Cyramza as First Genome-Driven Treatment for HCC

The U.S. Food and Drug Administration (FDA) approved ramucirumab ( Cyramza ) monotherapy for the treatment of hepatocellular carcinoma (HCC) in patients who have an alpha fetoprotein (AFP) of ≥400 ng/mL and have been previously treated with sorafenib. This is the first genome-driven treatment for HCC.

The approval was based on results of the multinational, randomized, double-blind, placebo-controlled, multicenter, phase III REACH‑2 study, which included 292 patients (median age = 64 years) with advanced HCC with AFP ≥400 ng/mL whose disease relapsed or was refractory to sorafenib. Patients were randomized 2:1 to receive ramucirumab 8 mg/kg plus best supportive care (BSC; n=197) or placebo plus BSC (n=95) every two weeks as an intravenous (IV) infusion until disease progression or unacceptable toxicity.

Interested to see which patients get this therapy compared with current treatments: FDA approves Cyramza for mCRC http://t.co/OOo60oYi17

— Dale Shepard MD, PhD (@ShepardDale) April 25, 2015

Ramucirumab Improves Overall Survival

Ramucirumab improved overall survival compared with placebo. The estimated median overall survival (primary endpoint) was 8.5 months (95% CI, 7.0-10.6) in the ramucirumab cohort and 7.3 months (95% CI, 5.4-9.1) in the placebo group (hazard ratio = 0.71; 95% CI, 0.53-0.95; P=0.020).

Median progression-free survival was 2.8 months and 1.6 months, respectively (P<0.0001). The overall response rate was 4.6% and 1.1%, respectively, and all responses were partial.

The most common adverse events (AEs) associated with ramucirumab were fatigue, peripheral edema, hypertension, abdominal pain, decreased appetite, proteinuria, nausea, and ascites. The most common laboratory abnormalities were hypoalbuminemia, hyponatremia, and thrombocytopenia. In the ramucirumab cohort, 18% of patients discontinued treatment due to AEs, most commonly because of proteinuria (2%).

Lilly receives fourth FDA approval for CYRAMZA (ramucirumab) http://t.co/bJjeG1XARq

— Victor Moreno (@VicMorenoGarcia) April 25, 2015

The recommended ramucirumab dose is 8 mg/kg IV every two weeks.

The FDA removed the boxed warning from the ramucirumab label, which noted a risk of hemorrhage, gastrointestinal perforation, and impaired wound healing with treatment. However, the updated label continues to provide information on these specific risks.